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Consensus Statement on Immunotherapy for the Treatment of Multiple Myeloma

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Consensus Statement on Immunotherapy for the Treatment of Multiple Myeloma Open access Position article and guidelines J Immunother Cancer: first published as 10.1136/jitc-2020-000734 on 12 July 2020. Downloaded from The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma Nina Shah,1 Jack Aiello,2 David E Avigan,3 Jesus G Berdeja,4 Ivan M Borrello,5 Ajai Chari,6 Adam D Cohen,7 Karthik Ganapathi,8 Lissa Gray,9 Damian Green,10 Amrita Krishnan,11 Yi Lin,12,13 Elisabet Manasanch,14 Nikhil C Munshi,15 Ajay K Nooka,16 Aaron P Rapoport,17 Eric L Smith,18 Ravi Vij,19 Madhav Dhodapkar20 To cite: Shah N, Aiello J, ABSTRACT disease (MRD) with a high degree of sensi- Avigan DE, et al. The Society Outcomes in multiple myeloma (MM) have improved tivity using multicolor flow cytometry (MFC) for Immunotherapy of Cancer dramatically in the last two decades with the advent of consensus statement on or next- generation sequencing (NGS) tech- novel therapies including immunomodulatory agents 9 immunotherapy for the nologies may further enhance the selection (IMiDs), proteasome inhibitors and monoclonal antibodies. treatment of multiple myeloma. of treatment strategies both at initial diagnosis In recent years, immunotherapy for the treatment of MM Journal for ImmunoTherapy and relapse. Despite these breakthroughs, has advanced rapidly, with the approval of new targeted of Cancer 2020;8:e000734. however, MM remains largely incurable, with doi:10.1136/jitc-2020-000734 agents and monoclonal antibodies directed against myeloma cell- surface antigens, as well as maturing data the vast majority of patients experiencing relapse at some point. ► Additional material is from late stage trials of chimeric antigen receptor (CAR) T published online only. To view, cells. Therapies that engage the immune system to treat Advances in understanding of the basic please visit the journal online myeloma offer significant clinical benefits with durable mechanisms of immune evasion and suppres- (http:// dx. doi. org/ 10. 1136/ jitc- responses and manageable toxicity profiles, however, sion in MM has led to new therapies with 2020- 000734). the appropriate use of these immunotherapy agents can demonstrated benefits for patients. In present unique challenges for practicing physicians. 2015, the US Food and Drug Administra- Accepted 01 June 2020 Therefore, the Society for Immunotherapy of Cancer tion (FDA) approved two mAbs for the http://jitc.bmj.com/ convened an expert panel, which met to consider the treatment of MM, daratumumab (dara) current role of approved and emerging immunotherapy 10 11 agents in MM and provide guidance to the oncology and elotuzumab, blazing a trail for the community by developing consensus recommendations. development of numerous other immuno- As immunotherapy evolves as a therapeutic option for the therapies in this disease setting, including 12–15 treatment of MM, these guidelines will be updated. chimeric antigen receptor (CAR) T cells, 16–18 antibody- drug conjugates (ADCs), bispe- on September 26, 2021 by guest. Protected copyright. cific T- cell engagers (BiTEs)19–21 and cancer 22 23 INTRODUCTION vaccines. As the world’s leading non- Multiple myeloma (MM) is the second most profit member-driven organization dedicated commonly diagnosed hematological malig- to advancing cancer immunotherapy, the nancy, with nearly 160 000 new cases world- Society for Immunotherapy of Cancer (SITC) wide in 2018.1 Before the 21st century, most develops Cancer Immunotherapy Guidelines patients with MM died within a few years for a variety of disease states. Previously, SITC © Author(s) (or their after diagnosis, yet outcomes have improved published the first-ever consensus statement employer(s)) 2020. Re- use dramatically during the past two decades. for the use of immunotherapy to treat hema- permitted under CC BY-NC. No Novel therapies including immunomodula- tological malignancies in 2016.24 commercial re- use. See rights and permissions. Published by tory agents (IMiDs), proteasome inhibitors Immunotherapy is currently playing BMJ. (PIs) and monoclonal antibodies (mAbs) a pivotal role in MM treatment, neces- For numbered affiliations see have been incorporated into standard treat- sitating clinical practice guidelines with end of article. ment approaches, which had previously been detailed recommendations specific to these limited to stem cell transplants, alkylating important, practice- changing modalities. Correspondence to 2–6 Dr Madhav Dhodapkar; agents and steroids. Additionally, advances Recognizing the rapid pace of advance- 7 8 madhav. v. dhodapkar@ emory. in risk stratification based on cytogenetics as ment of the field, and a need to update the edu well as the ability to detect minimal residual previously published consensus statement Shah N, et al. J Immunother Cancer 2020;8:e000734. doi:10.1136/jitc-2020-000734 1 Open access J Immunother Cancer: first published as 10.1136/jitc-2020-000734 on 12 July 2020. Downloaded from with practical guidance on how to incorporate the ever- conflicts of interest are readily reported. Recommenda- growing number of immunotherapeutic agents that tions are based on literature evidence, where possible, have been approved or are in the final stages of clinical and clinical experience, where appropriate.26 For trans- development into the treatment of MM, SITC convened parency, a draft of this consensus statement was made an expert panel encompassing perspectives from hema- publicly available for comment after journal submission. tology, medical oncology, hematopathology, nursing and All comments were considered for inclusion into the patient advocacy to provide evidence-based recommen- final manuscript. This consensus statement is intended to dations for the oncology community. This panel met to provide guidance and is not a substitute for the profes- consider issues related to patient selection, dosing and sional judgment of individual treating physicians. monitoring, toxicity management and quality of life (QoL), with the goal of preparing a consensus statement Evidence and consensus ratings on clinical use of immunotherapy for patients with MM. Consensus recommendations were derived from evidence In recognition of the rapid pace of advancement of within the published literature along with responses to a the immunotherapy field, this consensus statement clinical questionnaire that addressed current practices in will discuss emerging therapies that have not yet, at the the use or recommendation for use of immunotherapy time of publication, received United States Food and agents (online supplementary file 1). SITC Cancer Drug Administration approval. As such, the manuscript Immunotherapy Guidelines provide recommendations is divided into two sections, based on FDA approval based on peer- reviewed literature and consensus within status at time of publication. Because recommendations the expert panel. Consensus was defined as ≥75% agree- concerning the use of IMiDs were published in the 2016 ment among expert panel members. consensus statement on hematological malignancies,24 those agents are not extensively discussed in these guide- Conflicts of interest policy lines, except as components of combination regimens As per SITC policy, expert panel members managed with antibody therapies. Additionally, although alloge- potential competing interests through disclosure of all neic hematopoietic stem cell transplantation (allo-HSCT) financial relationships that might result in actual, poten- is an important therapeutic option in the management of tial or perceived conflicts of interest. No commercial MM, other groups have published consensus recommen- funding was provided to support the expert panel, litera- dations regarding its use25 and therefore a discussion of ture review, or the preparation of this manuscript. the approach was beyond the scope of these guidelines. As with any consensus statement, the recommendations Literature review process contained within this paper are intended to provide guid- The MEDLINE database was used to search the scientific ance and are not a substitute for the professional judg- literature for current therapies related to MM and immu- ment of individual physicians treating individual patients. notherapy in humans and encompassed articles published from 2012 to 2019, including clinical trials, meta- analyses, http://jitc.bmj.com/ practice guidelines and research in humans. The search MATERIALS AND METHODS terms included ‘multiple myeloma’ AND ‘immuno- SITC Multiple Myeloma Immunotherapy Guideline Expert Panel therapy’, ‘daratumumab’, ‘elotuzumab’, ‘isatuximab’, The SITC Multiple Myeloma Immunotherapy Guideline ‘CAR T cell therapy’, ‘bispecific antibody’, ‘antibody-drug Expert Panel consisted of 19 participants, including 17 conjugate’ and ‘quality of life.’ Articles were screened by medical oncologists, 1 nurse practitioner and 1 patient expert panel members to include only papers with clin- on September 26, 2021 by guest. Protected copyright. advocate. One hundred percent of clinical expert panel ically accurate and relevant information and to remove members reported previous experience/knowledge duplicate articles from independent searches, resulting regarding the use of immuno- oncology therapy for the in a final citation list cataloged using EndNote X9. The treatment of patients with MM. The panel communi- citation list was supplemented with additional articles cated regularly via email and teleconference in addition identified by the panel, as appropriate and necessary for to completing online
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